RSS-Feed abonnieren
DOI: 10.1055/s-0032-1331927
Elastography-based analysis of variants identified by a genome-wide association study as genetic determinants of liver enzyme activities
Background: Recent genome-wide study (GWAS) in over 61,000 individuals identified a set of loci that determine serum activities of liver enzymes [1]. Interestingly, only two variants, which are localized in the C6orf142 and TRIB1 gene loci, simultaneously increased the serum activities of ALT, AST and GGT [1]. Here we investigate these C6orf142 and TRIB1 variants as potential risk factors for increased liver stiffness in patients with chronic liver diseases (CLD).
Patients and methods: In total 899 individuals with CLD (age 20–86 years, 548 males) were recruited. Liver fibrosis was phenotyped non-invasively by transient elastography (TE, Fibroscan) [2]. The single nucleotide polymorphisms (SNPs) C6orf142 rs9296736 and TRIB1 rs2954021 were genotyped using PCR-based assays with 5'-nuclease and fluorescence detection.
Results: The genotype frequencies of the C6orf142 ([CC]=420, [CT]=368, [TT]=107) and TRIB1 variants ([AA]=229, [AG]=417, [GG]=246) do not differ from the frequencies deposited in the Entrez database. Case-control association analyses did not provide evidence for associations between the variants and low (i.e., <7.5 kPa) or advanced (i.e., >17.5 kPa) liver stiffness in the whole cohort or in analyses restricted to patients with viral and non-viral liver diseases (all P>0.05). Moreover, regression analysis demonstrated that alcohol consumption (P<0.01) and age (P<0.001) but neither the C6orft142 nor the TRIB1 SNP substantially increase liver stiffness values in our cohort.
Conclusions: The C6orft142 and TRIB1 variants, although associated with increased serum liver enzyme activities, do not affect liver stiffness in patients with CLD. These results indicate that distinct sets of genetic determinants affect specific hepatic pathways in healthy and diseased liver.
1. Chambers JC, et al. Nat Genet 2011.
2. Krawczyk M, et al. J Hepatol 2011.